深度学习将机械模型与单细胞转录组学数据联系起来,揭示了对DNA损伤的反应中的转录爆发
Zhiwei Huang1,2, Songhao Luo3, Zihao Wang1,2
1Guangdong Province Key Laboratory of Computational Science, Sun Yat-sen University, Guangzhou, China.
eLife
|March 4, 2026
概括
DeepTX是一个新的深度学习框架,从单细胞RNA测序数据中推断出全基因组的转录爆发. 这揭示了基因表达动态或转录爆发如何影响DNA损伤后的细胞命运决定.
科学领域:
- 分子生物学分子生物学
- 基因组学就是基因组学.
- 计算生物学 计算生物学
背景情况:
- 细胞利用静态基因表达程序来决定命运,例如分化或亡.
- 了解全基因组转录突破对DNA损伤的反应是一个挑战.
研究的目的:
- 开发一个可解释和可扩展的深度学习框架 (DeepTX) 来从单细胞RNA测序 (scRNA-seq) 数据中推断全基因组转录突发动力学.
- 将机械模型与scRNA-seq数据连接起来,以分析转录突破动态.
主要方法:
- 开发了DeepTX,这是一个集机械模型和scRNA-seq数据的深度学习框架.
- 将DeepTX应用于DNA损伤药物治疗中的scRNA-seq数据集.
- 推断了全基因组的转录突发动力学,并分析了它们与细胞命运的相关性.
主要成果:
- 从scRNA-seq数据中,DeepTX准确地推断出转录突发动力学.
- 不同的DNA损伤药物诱导了不同的转录突破模式.
- 5'--2'-脱氧氨治疗增加了爆发大小,与差异化相关.
- 5-甲治疗调节了爆发频率,与亡或生存相关.
结论:
- DeepTX能够从单细胞转录组学中推断全基因组的转录爆发.
- 转录性爆发动态与DNA损伤后的细胞命运决定有关.
- 该框架可以产生关于爆发动态和细胞命运之间的关系的假设.
相关概念视频
Overview of DNA Repair
In order to be passed through generations, genomic DNA must be undamaged and error-free. However, every day, DNA in a cell undergoes several thousand to a million damaging events by natural causes and external factors. Ionizing radiation such as UV rays, free radicals produced during cellular respiration, and hydrolytic damage from metabolic reactions can alter the structure of DNA. Damages caused include single-base alteration, base dimerization, chain breaks, and cross-linkage.
Chemically...
Chemically...
DNA Damage can Stall the Cell Cycle
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
DNA Damage Can Stall the Cell Cycle
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...


